Impact of common risk factors of fibrosis progression in chronic hepatitis C. Issue 10 (11th September 2014)

• Record Type: Journal Article
• Authors: Rüeger, S; Bochud, P-Y; Dufour, J-F; Müllhaupt, B; Semela, D; Heim, M H; Moradpour, D; Cerny, A; Malinverni, R; Booth, D R; Suppiah, V; George, J; Argiro, L; Halfon, P; Bourlière, M; Talal, A H; Jacobson, I M; Patin, E; Nalpas, B; Poynard, T; Pol, S; Abel, L; Kutalik, Z; Negro, F
• Is Part Of: Gut. Volume 64:Issue 10(2015)
• Page Start: 1605
• Page End: 1615
• Publication Date: 2014-09-11
• Subjects: HEPATITIS C -- CIRRHOSIS -- FIBROSIS; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2014-306997
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. Design: We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. Results: Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 ( TULP1 ), rs738409 ( PNPLA3 ), rs4374383 ( MERTK ) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. Conclusions: Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.